3-HYDROXYOCTANOIC, 6-HYDROXYOCTANOIC AND 7-HYDROXYOCTANOIC ACIDS ARE METABOLITES OF MEDIUM-CHAIN TRIGLYCERIDES AND EXCRETED IN URINE AS GLUCURONIDES

Three new metabolites of medium-chain fatty acid oxidation, 3-, 6- and 7-hydroxyoctanoyl beta-D-glucuronide, were identified in the urine of six infants who were fed a diet enriched in medium-chain triglyceride s (MCT), Glucuronides were extracted from the urine by organic solvent extraction with ethyl acetate and by solid-phase extraction on Sep-Pa k C-18 cartridges. The compounds of interest were also purified from t he organic solvent extract by preparative one-dimensional thin-layer c hromatography. Cleavage of the glucuronides was achieved by either alk aline hydrolysis or enzymatic hydrolysis with beta-D-glucuronidase. Th e analyses of the trimethylsilylated derivatives were performed both b y gas chromatography with dame ionization detection (GC/FID) and by ga s chromatography/mass spectrometry (GC/MS). The structure of the hydro xyoctanoic acids was proved by comparison of their mass spectra with t hose of reference substances. Authentic 6-hydroxyoctanoic acid was syn thesized. The presence of 6-hydroxyoctanoyl glucuronide shows that in addition to beta-oxidation, omega-oxidation and (omega - 1)-hydroxylat ion, medium-chain fatty acids can be oxidized at the omega-2 position, The conjugation of medium-chain hydroxymonocarboxylic acids with gluc uronic acid has not been described in humans before.